Spontaneous T-cell lymphokine production and enhanced macrophage la expression and tumoricidal acitivity in MRL-Ipr mice

Three macrophage functions were studied in MRL-Ipr mice with autoimmune lymphoproliferative disease: surface expression of I-region-associated (Ia) antigens, tumor cytotoxicity, and interleukin-1 (IL-1) production. MRL-Ipr mice had a significantly increased representation of Ia-positive macrophages in the peritoneal cavity, compared to all normal strains of mice. In order to study the basis of this increase, thymocytes or splenocytes from MRL-Ipr mice were transplanted intraperitoneally into normal mice. Three days later the recipient mice had peritoneal exudates rich in Ia-positive macrophages. The cells which induced this response were T cells which elaborated a lymphokine responsible for the recruitment of Ia-positive macrophages. In previous studies from our laboratory using normal mice, lymphokine was secreted only following the interaction of immune T cells with antigen. The resident macrophages of MRL-Ipr mice were activated and killed tumor cells if triggered by an interaction with bacterial products, even without the addition of lymphokines. Secretion of IL-1 was normal. Our results indicate that the diseased MRL-1pr mice are characterized by (i) activated T cells that spontaneously secrete macrophage stimulatory molecules; and (ii) activated macrophages that show both an increased expression of Ia and lymphokine-independent triggering of tumoricidal activity.